Effects of Arousal and Stress in Anxiety

National Institute of Mental Health (NIMH)1,418 enrolled

Overview

This study has several parts. One part will examine the influence of factors such as personality and past experience on reactions to unpleasant stimuli. Others will examine the effect of personality and emotional and attentional states on learning and memory. When confronted with fearful or unpleasant events, people can develop fear of specific cues that were associated with these events as well as to the environmental context in which the events occurred via a process called classical conditioning. Classical conditioning has been used to model anxiety disorders, but the relationship between stress and anxiety and conditioned responses remains unclear. This study will examine the relationship between cued conditioning and context conditioning . This study will also explore the acquisition and retention of different types of motor, emotional, and cognitive associative processes during various tasks that range from mildly arousing to stressful.

Objective: Fear and anxiety are adaptive responses to different types of threats. Fear is a short-duration response evoked by explicit threat cues and anxiety a more sustained state of apprehension evoked by unpredictable threat. This protocol studied fear using Pavlovian fear conditioning in two studies. Studies 1 and 3. Study 2 focused on anxiety. Studies 1 and 3 will be discontinued to focus uniquely on the study of anxiety. Specifically, we will examine the interactions between anxiety induced experimentally using verbal threat and cognitive processes. We will seek to 1) characterize the effect of anxiety on key cognitive processes including working memory and attention control and 2) examine the extent to which performance of cognitive tasks distract from anxiety. Study population: This more-than-minimal-risk protocol will test medically and psychiatrically healthy volunteers aged 18-50. Pregnant or nursing women will be excluded. Method: Fear and anxiety will be measured using the startle reflex to brief and loud sounds. Fear conditioning will be assessed using shock as unconditioned stimulus. Cognitive performance will be examined during periods of unpredictable shock anticipation. Outcome measures: The study will include cognitive performance and measure of aversive states, primarily the startle reflex.

Study Type

INTERVENTIONAL

Allocation

Purpose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

* INCLUSION CRITERIA: * Males and females * Age 18-50 EXCLUSION CRITERIA: * Pregnancy * Any current ongoing medical illness * Current Axis I disorders * Past significant psychiatric disorders (e.g., psychotic disorders) according to Diagnostic and Statistical Manual (DSM)-IV * Current alcohol or substance abuse according to DSM-IV criteria * History of alcohol or substance dependence based on DSM-IV criteria within 6 months prior to screening * Current psychotropic medication use * Current or past organic central nervous system disorders, including but not limited to seizure disorder or neurological symptoms of the wrist and arms (e.g., carpal tunnel syndrome). The latter exclusion is for shock studies only. * Positive urine toxicology screen * Employees of National Institute of Mental Health (NIMH) or an immediate family member of a NIMH employee.

Outcomes

Primary Outcomes

Go Correct Hits Followed by Button Press

Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 millisecond (ms) to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.

Time frame: 250 ms at a rate of one every 2000 ms

Nogo Trials Followed by no Button Press

Time frame: 250 ms at a rate of one every 2000 ms

Correct-go Reaction Time (RT)

Correct go responses were go trials followed by button press. Mean reaction time (RT) was calculated for correct-go to evaluate speed-accuracy trade-off.

Time frame: 2000 ms during trial

Response to Startle Reflex

The startle reflex was elicited with a 103-decibel (dB) white noise (40-ms duration) delivered via headphone. The eyeblink component of the startle reflex was recorded binaurally with two AgCl electrodes placed under the left eye. The peak startle/eyeblink reflex magnitude was determined in the 20-100 ms timeframe. The shock was administered either on the left wrist or on the left middle and ring fingers, depending on where the desired intensity was reached. Startle stimuli were delivered between two go trials and go trials that followed a startle stimulus were not included in the analysis. A shock was delivered in two of the four threat blocks in each sequence, just prior to the last go trial, which was not included in the analysis (for a total of 4 shocks). Shock could be administered only in the threat condition and never in the safe condition. The results were analyzed using a Condition (safe, threat) x Task (task, no task) repeated ANOVA.

Time frame: 20-100 ms window following the onset of the startle stimulus

Subjective Measures of Level of Anxiety

Subjects retrospectively rated their level of anxiety using a scale of 1-10 where 1 = "not at all anxious" and 10 = "extremely anxious" at the end of each block of a sequence for a total of eight blocks. A block was defined as a combination of a condition (safe or threat) and a task (task or no task). The results were analyzed using a Condition (safe, threat) x Task (task, no task) repeated ANOVA.

Time frame: Every 100 sec repeated 8 times

Secondary Outcomes

Measure of Attention Control

Subjects completed the Attention Control Scale (ACS) prior to start of the study. The ACS is a 20-item self-report scale that measures attentional focusing (9 items) and attentional shifting (11 items) rated on a four-point likert scale from "1 - almost never" to "4 - always" with total score range of 20 to 80. Higher score on ACS reflect better ability to direct and maintain attention.

Time frame: 1-3 weeks before start of study

Measure of Level of Anxiety

The level of anxiety was assessed using the Trait Anxiety Inventory questionnaire. The Trait Anxiety Scale (T-Anxiety) evaluates relatively stable aspects of "anxiety proneness", including general states of calmness, confidence, and security. The Trait Anxiety Scale has 20 items. All items are rated on a 4-point scale: 1 = almost never, 2 = sometimes, 3 = often, and 4 = almost always.. The scale has a minimum score of 20 and a maximum score of 80. Higher score indicates greater anxiety. Trait Anxiety score was measured prior to start of the study.